Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Registration Number
- NCT03755791
- Lead Sponsor
- Exelixis
- Brief Summary
This Phase 3 study evaluates the safety and efficacy of cabozantinib in combination with atezolizumab versus the standard of care sorafenib in adults with advanced hepatocellular carcinoma (HCC) who have not received previous systemic anticancer therapy. A single-agent cabozantinib arm will be enrolled in which subjects receive single agent cabozantinib in order to determine its contribution to the overall safety and efficacy of the combination with atezolizumab.
- Detailed Description
This is a multicenter, randomized, open-label, controlled Phase 3 trial of cabozantinib in combination with atezolizumab versus sorafenib in adults with advanced HCC who have not received previous systemic anticancer therapy in the advanced HCC setting. The primary objective of this study is to evaluate the effect of cabozantinib in combination with atezolizumab on the duration of progression-free survival (PFS) and duration of overall survival (OS) versus sorafenib. The secondary objective is to evaluate the activity of single-agent cabozantinib compared with sorafenib in this patient population.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 837
- Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients by CT or MRI per the AASLD 2018 or EASL 2018 guidelines.
- The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE).
- Measurable disease per RECIST 1.1 as determined by the Investigator.
- Barcelona Clinic Liver Cancer (BCLC) stage Category B or C.
- Child-Pugh Score of A.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Known fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
- Prior systemic anticancer therapy for advanced HCC including but not limited to chemotherapy, small molecule kinase inhibitors, and immune checkpoint inhibitors (ICIs). Subjects who have received local intratumoral or arterial chemotherapy are eligible; local anticancer therapy within ≥ 28 days before randomization
- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 8 weeks prior to randomization.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks prior to randomization.
- Concomitant anticoagulation with oral anticoagulants
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental arm Cabozantinib Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w Experimental arm Atezolizumab Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w Single-Agent Cabozantinib arm Cabozantinib Subjects with advanced HCC will receive cabozantinib 60 mg qd Control arm Sorafenib Subjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)
- Primary Outcome Measures
Name Time Method Duration of Progression Free Survival (PFS) for the experimental arm vs. the control arm Up to 27 months after the first subject is randomized. Defined as time from randomization to the earlier of progressive disease (PD) per RECIST 1.1 as determined by the Blinded Independent Radiology Committee (BIRC) or death from any cause. Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Duration of Overall Survival (OS) for the experimental arm vs. the control arm Up to 36 months after the first subject is randomized. Defined as time from randomization to date of death from any cause.
- Secondary Outcome Measures
Name Time Method Duration of Progression Free Survival (PFS) for the single-agent arm vs. the control arm Up to 20 months after the first subject is randomized. Duration of PFS per RECIST 1.1 by BIRC
Trial Locations
- Locations (245)
Exelixis Clinical Site #88
🇺🇸Philadelphia, Pennsylvania, United States
Exelixis Clinical Site #78
🇦🇺Camperdown, New South Wales, Australia
Exelixis Clinical Site #7
🇺🇸Burlington, Massachusetts, United States
Exelixis Clinical Site #195
🇺🇸Chicago, Illinois, United States
Exelixis Clinical Site #6
🇺🇸Baltimore, Maryland, United States
Exelixis Clinical Site #138
🇺🇦Uzhhorod, Ukraine
Exelixis Clinical Site #96
🇹🇭Pathum Wan, Bangkok, Thailand
Exelixis Clinical Site #70
🇬🇪Tbilisi, Georgia
Exelixis Clinical Site #134
🇲🇽San Luis Potosí, Mexico
Exelixis Clinical Site #67
🇬🇪Tbilisi, Georgia
Exelixis Clinical Site #206
🇷🇴Bucuresti, Romania
Exelixis Clinical Site #61
🇨🇭Zurich, Switzerland
Exelixis Clinical Site #116
🇸🇬Singapore, Singapore
Exelixis Clinical Site #119
🇨🇳Changhua, Taiwan
Exelixis Clinical Site #106
🇸🇬Singapore, Singapore
Exelixis Clinical Site #145
🇨🇳Tainan, Taiwan
Exelixis Clinical Site #129
🇬🇧London, England, United Kingdom
Exelixis Clinical Site #82
🇨🇳Taipei, Taiwan
Exelixis Clinical Site #83
🇬🇧Bristol, England, United Kingdom
Exelixis Clinical Site #151
🇬🇧London, England, United Kingdom
Exelixis Clinical Site #115
🇨🇭Basel, Switzerland
Exelixis Clinical Site #172
🇨🇭Bern, Switzerland
Exelixis Clinical Site #162
🇨🇳Kaohsiung, Taiwan
Exelixis Clinical Site #128
🇨🇳Taipei, Taiwan
Exelixis Clinical Site #161
🇨🇳Taichung, Taiwan
Exelixis Clinical Site #143
🇹🇭Chiang Mai, Thailand
Exelixis Clinical Site #224
🇨🇳Changsha, Hunan, China
Exelixis Clinical Site #242
🇨🇳Guangzhou, Guangdong, China
Exelixis Site #241
🇨🇳Changsha, Hunan, China
Exelixis Clinical Site #221
🇨🇳Nanchang, Jiangxi, China
Exelixis Clinical Site #185
🇨🇳Nanjing, Jiangsu, China
Exelixis Clinical Site #246
🇨🇳Changchun, Jilin, China
Exelixis Clinical Site #229
🇨🇳Changchun, Jilin, China
Exelixis Clinical Site #226
🇨🇳Linyi, Shandong, China
Exelixis Site #240
🇨🇳Shanghai, China
Exelixis Clinical Site #236
🇨🇳Shenyang, Liaoning, China
Exelixis Site #239
🇨🇳Beijing, China
Exelixis Clinical Site #218
🇨🇳Hangzhou, Zhejiang, China
Exelixis Clinical Site #223
🇨🇳Hangzhou, Zhejiang, China
Exelixis Clinical Site #58
🇺🇸Washington, District of Columbia, United States
Exelixis Clinical Site #54
🇺🇸San Francisco, California, United States
Exelixis Clinical Site #176
🇺🇸Portland, Oregon, United States
Exelixis Clinical Site #4
🇺🇸Atlanta, Georgia, United States
Exelixis Clinical Site #120
🇺🇸Chicago, Illinois, United States
Exelixis Clinical Site #1
🇺🇸Las Vegas, Nevada, United States
Exelixis Clinical Site #44
🇺🇸La Jolla, California, United States
Exelixis Clinical Site #3
🇺🇸Spokane, Washington, United States
Exelixis Clinical Site #213
🇦🇷City of Buenos Aires, Buenos Aires, Argentina
Exelixis Clinical Site #199
🇺🇸Dallas, Texas, United States
Exelixis Clinical Site #112
🇺🇸Los Angeles, California, United States
Exelixis Clinical Site #207
🇺🇸San Diego, California, United States
Exelixis Clinical Site #208
🇺🇸Phoenix, Arizona, United States
Exelixis Clinical Site #39
🇺🇸Toledo, Ohio, United States
Exelixis Clinical Site #154
🇺🇸Houston, Texas, United States
Exelixis Clinical Site #171
🇦🇺Kingswood, New South Wales, Australia
Exelixis Clinical Site #19
🇺🇸Temple, Texas, United States
Exelixis Clinical Site #46
🇺🇸Seattle, Washington, United States
Exelixis Clinical Site #109
🇺🇸San Francisco, California, United States
Exelixis Clinical Site #220
🇦🇷Rosario, Santa Fe, Argentina
Exelixis Clinical Site #201
🇦🇷Rosario, Santa Fe, Argentina
Exelixis Clinical Site #165
🇦🇺Darlinghurst, New South Wales, Australia
Exelixis Clinical Site #64
🇦🇹Linz, Oberosterreich, Austria
Exelixis Clinical Site #126
🇦🇺Kogarah, New South Wales, Australia
Exelixis Clinical Site #166
🇦🇺Heidelberg, Victoria, Australia
Exelixis Clinical Site #107
🇦🇺Box Hill, Victoria, Australia
Exelixis Clinical Site #142
🇦🇺Greenslopes, Queensland, Australia
Exelixis Clinical Site #137
🇦🇹St. Pölten, Lower Austria, Austria
Exelixis Clinical Site #17
🇦🇺Kurralta Park, South Australia, Australia
Exelixis Clinical Site #190
🇦🇺Nedlands, Western Australia, Australia
Exelixis Clinical Site #198
🇦🇹Graz, Steiermark, Austria
Exelixis Clinical Site #174
🇦🇹Wien, Austria
Exelixis Clinical Site #50
🇧🇪Brussels, California, Belgium
Exelixis Clinical Site #184
🇧🇷Salvador, BA, Brazil
Exelixis Clinical Site #113
🇧🇷Curitiba, PR, Brazil
Exelixis Clinical Site #156
🇧🇷São Paulo, SP, Brazil
Exelixis Clinical Site #187
🇧🇷São Paulo, SP, Brazil
Exelixis Clinical Site #194
🇨🇦Hamilton, Ontario, Canada
Exelixis Clinical Site #233
🇨🇳Hefei, Anhui, China
Exelixis Clinical Site #228
🇨🇳Fuzhou, Fujian, China
Exelixis Clinical Site #225
🇨🇳Xiamen, Fujian, China
Exelixis Clinical Site #230
🇨🇳Zhengzhou, Henan, China
Exelixis Clinical Site #231
🇨🇳Changsha, Hunan, China
Exelixis Clinical Site #234
🇨🇳Jiangyin, Jiansu, China
Exelixis Clinical Site #237
🇨🇳Beijing, China
Exelixis Clinical Site #130
🇨🇴Montería, Cordoba, Colombia
Exelixis Clinical Site #232
🇨🇳Shanghai, China
Exelixis Clinical Site #18
🇨🇿Hradec Králové, Czechia
Exelixis Clinical Site #37
🇨🇿Olomouc, Czechia
Exelixis Clinical Site #43
🇫🇷Amiens, France
Exelixis Clinical Site #27
🇫🇷Besancon, France
Exelixis Clinical Site #49
🇫🇷Montpellier, France
Exelixis Clinical Site #158
🇮🇹Bologna, Italy
Exelixis Clinical Site #31
🇫🇷Montbeliard, France
Exelixis Clinical Site #105
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #56
🇫🇷Bondy Cedex, France
Exelixis Clinical Site #29
🇫🇷Caen Cedex 09, France
Exelixis Clinical Site #16
🇫🇷Lyon Cedex 4, France
Exelixis Clinical Site #48
🇫🇷Clichy, France
Exelixis Clinical Site #55
🇫🇷Lille Cedex, France
Exelixis Clinical Site #69
🇬🇪Batumi, Georgia
Exelixis Clinical Site #66
🇬🇪Tbilisi, Georgia
Exelixis Clinical Site #68
🇬🇪Tbilisi, Georgia
Exelixis Clinical Site #26
🇭🇺Szeged, Hungary
Exelixis Clinical Site #140
🇭🇺Budapest, Hungary
Exelixis Clinical Site #244
🇩🇪Frankfurt, Hessen, Germany
Exelixis Clinical Site #214
🇩🇪Berlin, Germany
Exelixis Clinical Site #170
🇮🇪Dublin, Ireland
Exelixis Clinical Site #215
🇩🇪Hamburg, Germany
Exelixis Clinical Site #114
🇰🇷Busan, Korea, Republic of
Exelixis Clinical Site #135
🇲🇽León, Guanajuato, Mexico
Exelixis Clinical Site #127
🇰🇷Suwon, Gyeonggi-do, Korea, Republic of
Exelixis Clinical Site #99
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #30
🇮🇱Jerusalem, Israel
Exelixis Clinical Site #152
🇮🇹Brescia, Italy
Exelixis Clinical Site #131
🇮🇹Novara, Italy
Exelixis Clinical Site #177
🇮🇹Torino, Italy
Exelixis Clinical Site #40
🇮🇱Ramat-Gan, Israel
Exelixis Clinical Site #33
🇮🇱Petah Tikva, Israel
Exelixis Clinical Site #163
🇮🇹Tricase, Lecce, Italy
Exelixis Clinical Site #35
🇮🇱Rehovot, Israel
Exelixis Clinical Site #182
🇮🇹Torino, Italy
Exelixis Clinical Site #75
🇰🇷Incheon, Korea, Republic of
Exelixis Clinical Site #141
🇲🇽Tuxtla Gutiérrez, Chiapas, Mexico
Exelixis Clinical Site #133
🇲🇽Ciudad De México, Mexico
Exelixis Clinical Site #160
🇲🇽Mexico City, Mexico
Exelixis Clinical Site #79
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #132
🇲🇽Monterrey, Nuevo Leon, Mexico
Exelixis Clinical Site #92
🇳🇱Maastricht, Limburg, Netherlands
Exelixis Clinical Site #118
🇵🇭Cebu City, Philippines
Exelixis Clinical Site #60
🇳🇿Grafton, Auckland, New Zealand
Exelixis Clinical Site #211
🇷🇴Cluj-Napoca, Cluj, Romania
Exelixis Clinical Site #202
🇷🇴Cluj-Napoca, Cluj, Romania
Exelixis Clinical Site #84
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Exelixis Clinical Site #36
🇳🇱Utrecht, Netherlands
Exelixis Clinical Site #136
🇵🇭Quezon City, Philippines
Exelixis Clinical Site #41
🇵🇱Warszawa, Mazowieckie, Poland
Exelixisi Clinical Site #100
🇨🇳Taipei, Taiwan
Exelixis Clinical Site #147
🇮🇹Milan, Italy
Exelixis Clinical Site #149
🇮🇹Napoli, Italy
Exelixis Clinical Site #167
🇮🇹Roma, Italy
Exelixis Clinical Site #34
🇨🇦Winnipeg, Manitoba, Canada
Exelixis Clinical Site #71
🇨🇦Calgary, Alberta, Canada
Exelixis Clinical Site #222
🇨🇦Halifax, Nova Scotia, Canada
Exelixis Clinical Site #212
🇨🇦Ottawa, Ontario, Canada
Exelixis Clinical Site #85
🇨🇦Montréal, Quebec, Canada
Exelixis Clinical Site #47
🇫🇷Nantes, France
Exelixis Clinical Site #51
🇫🇷Nice, France
Exelixis Clinical Site #20
🇫🇷Pessac, France
Exelixis Clinical Site #32
🇫🇷Vandœuvre-lès-Nancy, France
Exelixis Clinical Site #89
🇧🇷Belo Horizonte, MG, Brazil
Exelixis Clinical Site #98
🇧🇷Belo Horizonte, MG, Brazil
Exelixis Clinical Site #181
🇧🇷São Paulo, SP, Brazil
Exelixis Clinical Site #91
🇧🇷São Paulo, Brazil
Exelixis Clinical Site #104
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #38
🇨🇿Praha 5, Czechia
Exelixis Clinical Site #72
🇦🇺Parkville, Victoria, Australia
Exelixis Clinical Site #62
🇳🇿Newton, Wellington, New Zealand
Exelixis Clinical Site #216
🇦🇷City of Buenos Aires, Buenos Aires, Argentina
Exelixis Clinical Site #219
🇦🇷Pilar, Buenos Aires, Argentina
Exelixis Clinical Site #5
🇺🇸Kansas City, Missouri, United States
Exelixis Clinical Site #76
🇺🇸Albuquerque, New Mexico, United States
Exelixis Clinical Site #8
🇺🇸Saint Louis, Missouri, United States
Exelixis Clinical Site #210
🇩🇪Kassel, Hessen, Germany
Exelixis Clinical Site #200
🇺🇸Orange, California, United States
Exelixis Clinical Site #2
🇺🇸Rialto, California, United States
Exelixis Clinical Site #191
🇺🇸Miami, Florida, United States
Exelixis Clinical Site #11
🇺🇸Kansas City, Missouri, United States
Exelixis Clinical Site #14
🇺🇸New Brunswick, New Jersey, United States
Exelixis Clinical Site #12
🇺🇸Chapel Hill, North Carolina, United States
Exelixis Clinical Site #13
🇺🇸Seattle, Washington, United States
Exelixis Clinical Site #144
🇺🇸Charleston, South Carolina, United States
Exelixis Clinical Site #217
🇦🇷City of Buenos Aires, Buenos Aires, Argentina
Exelixis Clinical Site #155
🇦🇺Westmead, New South Wales, Australia
Exelixis Clinical Site #150
🇦🇹Klagenfurt, Kärnten, Austria
Exelixis Clinical Site #102
🇧🇪Liège, Belgium
Exelixis Clinical Site #121
🇧🇷Jaú, SP, Brazil
Exelixis Clinical Site #175
🇧🇷Barretos, SP, Brazil
Exelixis Clinical Site #203
🇧🇷Porto Alegre, RS, Brazil
Exelixis Clinical Site #186
🇧🇷São Paulo, SP, Brazil
Exelixis Clinical Site #227
🇨🇳Harbin, Heilongjiang, China
Exelixis Clinical Site #238
🇨🇳Nanchang, Jiangxi, China
Exelixis Clinical Site #235
🇨🇳Chengdu, Sichuan, China
Exelixis Clinical Site #10
🇨🇿Praha 4, Czechia
Exelixis Clinical Site #23
🇫🇷Grenoble, France
Exelixis Clinical Site #9
🇭🇰Hong Kong, Hong Kong
Exelixis Clinical Site #25
🇭🇺Debrecen, Hungary
Exelixis Clinical Site #53
🇮🇹Rozzano, Milano, Italy
Exelixis Clinical Site #157
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Exelixis Clinical Site #243
🇮🇹Udine, Italy
Exelixis Clinical Site #77
🇰🇷Busan, Korea, Republic of
Exelixis Clinical Site #86
🇰🇷Busan, Korea, Republic of
Exelixis Clinical Site #93
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #52
🇳🇱Amsterdam, Noord-Holland, Netherlands
Exelixis Clinical Site #153
🇲🇽Veracruz, Mexico
Exelixis Clinical Site #117
🇵🇭Pasig City, Philippines
Exelixis Clinical Site #24
🇵🇱Gdansk, Pomorskie, Poland
Exelixis Clinical Site #204
🇷🇴Cluj-Napoca, Cluj, Romania
Exelixis Clinical Site #209
🇷🇴Iaşi, Romania
Exelixis Clinical Site #74
🇷🇺Kislino, Kursk Region, Russian Federation
Exelixis Clinical Site #81
🇷🇺Kaluga, Russian Federation
Exelixis Clinical Site #95
🇷🇺Krasnodar, Russian Federation
Exelixis Clinical Site #108
🇷🇺Moscow, Russian Federation
Exelixis Clinical Site #111
🇷🇺Saint Petersburg, Russian Federation
Exelixis Clinical Site #101
🇷🇺Murmansk, Russian Federation
Exelixis Clinical Site #90
🇷🇺Saint-Petersburg, Russian Federation
Exelixis Clinical Site #80
🇷🇺Nizhny Novgorod, Russian Federation
Exelixis Clinical Site #73
🇷🇺Sochi, Russian Federation
Exelixis Clinical Site #97
🇸🇬Singapore, Singapore
Exelixis Clinical Site #21
🇪🇸Majadahonda, Madrid, Spain
Exelixis Clinical Site #28
🇪🇸Santander, Cantabria, Spain
Exelixis Clinical Site #22
🇪🇸Majadahonda, Madrid, Spain
Exelixis Clinical Site #59
🇪🇸Pamplona, Navarra, Spain
Exelixis Clinical Site #103
🇪🇸Barcelona, Spain
Exelixis Clinical Site #168
🇪🇸Valencia, Spain
Exelixis Clinical Site #164
🇪🇸Madrid, Spain
Exelixis Clinical Site #63
🇪🇸Madrid, Spain
Exelixis Clinical Site #45
🇪🇸Zaragoza, Spain
Exelixis Clinical Site #110
🇨🇭Saint Gallen, Switzerland
Exelixis Clinical Site #197
🇨🇳Tainan City, Taiwan
Exelixis Clinical Site #94
🇨🇳Taoyuan, Taiwan
Exelixis Clinical Site #139
🇹🇭Hat Yai, Songkla, Thailand
Exelixis Clinical Site #183
🇹🇭Khon Kaen, Thailand
Exelixis Clinical Site #173
🇹🇷Edirne, Turkey
Exelixis Clinical Site #125
🇺🇦Chernivtsi, Ukraine
Exelixis Clinical Site #178
🇹🇷Ankara, Turkey
Exelixis Clinical Site #179
🇹🇷Istanbul, Turkey
Exelixis Clinical Site #189
🇹🇷Istanbul, Instanbul, Turkey
Exelixis Clinical Site #193
🇹🇷Ankara, Turkey
Exelixis Clinical Site #122
🇺🇦Dnipro, Ukraine
Exelixis Clinical Site #180
🇹🇷Malatya, Turkey
Exelixis Clinical Site #124
🇺🇦Odesa, Ukraine
Exelixis Clinical Site #123
🇺🇦Kharkiv, Ukraine
Exelixis Clinical Site #87
🇬🇧Cambridge, England, United Kingdom
Exelixis Clinical Site #196
🇬🇧Belfast, Northern Ireland, United Kingdom
Exelixis Clinical Site #192
🇬🇧Manchester, England, United Kingdom
Exelixis Clinical Site #15
🇵🇱Mysłowice, Slaskie, Poland
Exelixis Clinical Site #65
🇧🇪Brussels, Belgium
Exelixis Clinical Site #188
🇧🇪Leuven, Belgium
Exelixis Clinical Site #169
🇧🇪Edegem, Belgium
Exelixis Clinical Site #148
🇧🇪Gent, Belgium
Exelixis Clinical Site #57
🇧🇪Haine-Saint-Paul, Belgium
Exelixis Clinical Site #159
🇺🇸Tucson, Arizona, United States
Exelixis Clinical Site #205
🇨🇦Edmonton, Alberta, Canada
Exelixis Clinical Site #146
🇭🇰Hong Kong, Hong Kong
Exelixis Clinical Site #42
🇭🇰Hong Kong, Hong Kong